AB0437 IMMUNOGENICITY ANALYSIS FROM THE VOLTAIRE TRIALS IN PATIENTS WITH RHEUMATOID ARTHRITIS, CROHN’S DISEASE, AND CHRONIC PLAQUE PSORIASIS
Authors: V. Strand, S. Bender, D. Mccabe
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The VOLTAIRE trials program compared safety, efficacy, and immunogenicity of biosimilar BI 695501 with adalimumab reference product (RP) for indications including moderate-severely active rheumatoid arthritis (RA), Crohn's disease (CD), and chronic plaque psoriasis (PsO). Details of each active-comparator, randomized controlled trial (RCT) are published. <sup>[1,2,3]</sup> <h3>Objectives</h3> Here we compare immunogenicity across these indications and by patient sex. <h3>Methods</h3> Immunogenicity was assessed at various timepoints by the proportion of patients with anti-drug antibodies (ADAs) and neutralising antibodies (nAbs), using acid dissociation followed by an electrochemiluminescence assay (ECL; MSD platform; Meso Scale Diagnostics LLC, USA).<sup>[4]</sup> Assay sensitivity was 50 ng/mL, and drug tolerance ≥30 μg/mL (free drug) at the low positive control level. <h3>Results</h3> Data are presented in <b>Table 1</b>. <h3>Conclusion</h3> Minor differences in immunogenicity (ADAs, ADA titres and nAbs) between BI 695501 and adalimumab RP were observed across these 3 indications. The proportion of ADA- and nAb-positive patients increased from baseline in all 3 RCTs, and were similar in RA and CD RCTs, but rates were higher in PsO RCT. Subgroup analysis by patient sex showed the same trend. These differences may be partially explained by concomitant background therapy (MTX) in RA trial, stable doses of AZA, 6-MP or MTX in 36% of CD patients and the absence of background therapy in PsO RCT. Comparisons are limited by different visit schedules in the trials. Historical comparisons to RP data are complicated by recent differences in regulatory requirements for increased ADA assay sensitivity and stringency for biosimilar products than those originally used for the RP. Acid dissociation followed by the more sensitive ECL assay for detection of ADAs is not dependent on serum drug concentrations. In conclusion, these analyses confirm the biosimilarity of BI 695501 with the adalimumab RP across RA, CD, and PsO. <h3>References</h3> [1] Cohen SB, et al. Ann Rheum Dis. 2018;77:91-21. [2] Hanauer S, et al. Lancet Gastroenterol Hepatol. 2021;6:816-25. [3] Menter A, et al. Expert Opin Biol Ther. 2021;21:87-96. [4] Wynne C, et al. Expert Opin Inv Drugs 2016;25:1361-70. <h3>Acknowledgements</h3> The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. The authors received no direct compensation related to the development of the abstract. Writing support was provided by Debra Brocksmith, MB ChB, PhD, of Elevate Scientific Solutions (Envision Pharma Group), which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). BIPI was given the opportunity to review the abstract for medical and scientific accuracy. <h3>Disclosure of Interests</h3> Vibeke Strand Consultant of: AbbVie, Amgen, Aria, AstraZeneca, Bayer, Bioventus, Blackrock, BMS, Boehringer Ingelheim, Celltrion, Chemocentryx, Equillium, Gilead, Genentech/Roche, Glenmark, GSK, Horizon, Inmedix, Janssen, Kiniksa, Kypha, Lilly, Merck, MiMedx, Novartis, Pfizer, Priovant, Regeneron, Rheos, R-Pharma, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sorrento, Spherix, and Tonix, Shaun Bender Employee of: Boehringer Ingelheim Pharmaceuticals, Inc. (previous employment), Dorothy McCabe Employee of: Boehringer Ingelheim Pharmaceuticals, Inc.